Lenvatinib-Based Combinations for Intermediate-/Poor-Risk mRCC


Thomas E. Hutson, DO, PharmD, of Texas Oncology, reacts to results demonstrated by the CLEAR study of lenvatinib in combination with pembrolizumab or everolimus for the treatment of metastatic renal cell carcinoma and discusses best practices for educating community oncologists on dosing with lenvatinib.

Sumanta Kumar Pal, MD: Tom, I saw you nodding your head a lot. What are your thoughts in terms of frontline intermediate- and poor-risk treatment?

Thomas E. Hutson, DO, PharmD: I agree with that. The CLEAR study certainly met all of what I would have chosen as my thresholds for what would change the standard of care. It has been only about 27 months of follow-up. We want to see that long term, see how the tails look, and see if we’re getting the amazing data that were just presented with ipilimumab-nivolumab. If we did start seeing that with an I/O [immuno-oncology]–TKI [tyrosine kinase inhibitor], then you have a winner.

What I like about the I/O–TKI for community oncologists who may not treat a lot of kidney cancer is that we really want them to be familiar with 1 regimen. To think that a community oncologist is going to know the nuances between all the different I/O–TKIs and be able to jump between 2 or 3 of them is probably not realistic. If we remember back in the TKI days, we wanted them to learn 1, know how to give it well, and how to handle adverse effects. The nice thing about the lenvatinib-pembrolizumab I/O–TKI is that it has a clinical benefit rate of 90% or above. That virtually means that everyone who gets it is going to have at least stable disease. That’s compelling. It doesn’t take a lot of extra effort for the community oncologist to get a drug that’s at least going to control the disease for the patient. I am a person who believes in I/O–I/O too, so I actually have the discussion with patients—just like in the day of high-dose IL-2. I used to do high-dose IL-2. I used to make sure my patients heard of it. In my practice, I/O–I/O is still the most common treatment I’m using in intermediate- and poor-risk disease, but my desire would be to start tilting more toward the lenvatinib-pembrolizumab as that becomes approved.

Sumanta Kumar Pal, MD: I’m going to ask you about that in a little more detail, Tom. You mentioned teaching community-based oncologists to get familiar with a drug that they may or may not know landed 12 mg—maybe 18 mg in the second-line setting for renal cell carcinoma. How do you teach them about 20 mg in the front line? I’m going to try not to stress too many of my biases, but getting up 20 mg and maintaining in the front line tends to be a bit of a challenge.

Thomas E. Hutson, DO, PharmD: It is. Between 18 mg and 20 mg, what’s the real difference? Those are problems that the company is certainly aware of. Most community oncologists may be familiar with that dosing from the gynecologic oncology arena. There are a lot of community oncologists treating patients in gynecologic oncology, so there may be at least some familiarity with that. But that is going to be 1 of the hurdles they face: getting people familiar with lenvatinib. From the Keytruda perspective, everyone is familiar with that. It’s just getting people familiar with the dosing on lenvatinib. That’s going to be an uphill battle.


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